Abstract

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. While specific mechanisms underlying SUDEP are not well understood, evidence suggests most SUDEP occurs due to seizure-induced respiratory arrest. SUDEP also tends to happen at night. While this may be due to circumstances humans find themselves in at night, such as being alone without supervision or sleeping prone, or due to independent influences of sleep state, there are a number of reasons why the night (i.e. circadian influences) could be an independent risk factor for SUDEP. We explored this possibility here. Adult male WT mice were instrumented for EEG, EMG and EKG recording and subjected to maximal electroshock (MES) seizures during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep during the nighttime/dark phase. These data were compared to data collected following seizures induced during the daytime/light phase. Seizures induced during the nighttime were similar in severity and duration compared to those induced during the daytime; however, seizures induced during the nighttime were associated with a lesser degree of respiratory dysregulation and post ictal EEG suppression. Seizures induced during REM sleep during the nighttime were universally fatal, as is seen when seizures are induced during REM during the daytime. Taken together these data implicate a role for time of day in influencing the physiological consequences of seizures that may contribute to seizure-induced death.